A leading Manchester scientist has been awarded a grant worth over £185,000 by Breast Cancer Now to investigate how breast cancer cells are able to hibernate for years before returning elsewhere in the body.

When breast cancer spreads – known as secondary breast cancer – it becomes incurable, and almost all of the 11,500 women that die as a result of breast cancer each year in the UK will have seen their cancer spread. More than 2,000 women in Greater Manchester are diagnosed with breast cancer every year, and over 400 women in the region die from the disease each year.

Special types of cancer cells, called cancer stem cells, are responsible for breast cancer coming back after treatment. These cells are able to travel to distant locations – such as the bone – where they remain inactive, not being affected by therapy, for long periods of time. For example, in a subtype of breast cancer called ER-positive breast cancer – which makes up 80% of all breast cancers – recurrence may happen years or decades after treatment. However, once cancer stem cells have ‘awakened’, they can grow into secondary tumours.

The bone is one of the most common and least treatable places for breast cancer to spread to. Secondary tumours in the bone can cause joint pain as well as debilitating fractures that often require surgery at a time that is already difficult for patients.

Dr Robert Clarke, based at the Breast Cancer Now Research Unit at the University of Manchester, has previously found that a protein called NOTCH is vital in helping breast cancer stem cells survive treatments. NOTCH has many different roles around the body, and Dr Clarke and his team believe that NOTCH could be critical in the hibernation and reawakening of breast cancer stem cells in locations like the bone, as well as other places.

In this study, Dr Clarke’s group will investigate the environment in the bone where breast cancer stem cells hibernate, and how NOTCH helps them to survive. The team will use ER-positive breast cancer cells that have been grown in the lab, as well as those that have been donated by patients with primary and secondary breast cancers.

Next, Dr Clarke will implant the breast cancer cells into mice to further examine the role of NOTCH. Using imaging technology, he will investigate how blocking this protein affects the spread of breast cancer cells to the bone. Finally, the team will study individual sleeping or re-awakened cancer stem cells, to understand which genes are activated in these cells, how NOTCH affects the cells’ activity, and how they are able to hibernate.

“If we are to stop people dying from breast cancer, we must stop it returning. One way to do this is to find ways to kill breast cancer stem cells.

“To do this we need to fully understand how these cells are able to hibernate for many years before reawakening to form secondary tumours.

“Dr Clarke’s research will help us address this question, and could eventually lead to ways to prevent secondary tumours from developing many years after treatment, ultimately stopping people dying from the disease.”

Dr Rob Clarke leads the Breast Cancer Now Manchester Research Unit, which has received generous donations from supporters including the Isle of Man Anti-Cancer Association, the Zochonis Charitable Trust, and Roger and Carol Allington.

1. Source of information: Local incidence and mortality survival statistics were provided on request by Public Health England, April 2017 – similar data are available from cancerdata.nhs.uk. Figures are based upon averages for 2012-2014.